Improved staging of lobular breast cancer with novel amino acid metabolic and tumor neovasculature receptor imaging Project Summary / Abstract Invasive lobular breast cancer (ILC) accounts for approximately 10-15% of breast malignancies and has an underlying metastatic rate of up to 43%. ILC has discohesive growth making metastasis difficult to visualize with conventional imaging modalities such as computed tomography (CT), bone scan, and magnetic resonance imaging (MR). Suboptimal imaging adversely impacts accurate staging upon which therapeutic decisions are based. While fluorodeoxyglucose (FDG) PET has been shown to clinically upstage patients with locally advanced IDC, this is not so with ILC, which has been described as ?initially indolent but slowly progressive?. There are no accurate imaging techniques for staging ILC. Our goal is to address an unmet public health need by improved staging of ILC, specifically detection of metastatic disease. Amino acid transporters are upregulated in breast cancer cells. We and others have successfully imaged breast cancer with fluciclovine (18F) PET, an FDA approved synthetic amino acid radiotracer originally developed at Emory for imaging of cerebral glioma and prostate cancer. In exploratory studies conducted at Emory and Memorial Sloan Kettering in 39 women with breast cancer (13 patients with ILC), fluciclovine PET demonstrated promising results in detection of ILC in primary tumors and locoregional metastases. Distant disease was not studied. There is emerging data that imaging with prostate specific membrane antigen (PSMA) PET may improve detection of breast cancer, including ILC. Prostate-specific is actually a misnomer as PSMA receptors are upregulated in tumor neovasculature in many cancers including breast cancer. PSMA targeting of lobular breast cancer for more effective staging has been strongly encouraged by experts in the field. We hypothesize that metabolic imaging with amino acid transporter PET will improve staging of ILC, particularly for distant metastases, compared to conventional imaging. We also hypothesize that receptor directed PSMA imaging of tumor associated neovasculature in ILC will reveal unique information to complement metabolic interrogation with fluciclovine PET. To test these hypotheses with the highest scientific rigor, we propose an early phase trial with fluciclovine and PSMA PET strategies centered on detection of metastasis in patients with advanced ILC using histology as the gold standard. As an exploratory aim, we will also correlate the occurrence of circulating tumor DNA (ctDNA) mutations including PIK3CA, ESR1, HER2, and AKT1 with presence of metastasis and tumor burden. We expect this study will generate sufficient preliminary data to determine feasibility for a definitive NIH sponsored multi-center trial developing more accurate staging techniques to alter current practice for imaging of ILC.
/Relevance Invasive lobular breast cancer (ILC) accounts for approximately 10-15% of breast malignancies and when it spreads is difficult to detect with current imaging tools, but our research group at Emory has shown that advanced molecular imaging based on increased amino acid use by breast cancer with a positron emission tomography (PET) radiotracer [fluciclovine (18F)] has shown promise in the detection of ILC spread. The overall goal of the current proposal is to build on these results in patients with ILC with suspicion of spread by determining if this amino acid based radiotracer [fluciclovine (18F)] or another PET radiotracer which detects tumor blood vessel growth [68Ga PSMA] can be used to better detect the spread of invasive lobular cancer compared with usual imaging such as bone scan, computerized tomography (CT) or magnetic resonance imaging (MR) scans. We will also be exploring a new direction of combining this information from PET imaging with a blood test called circulating tumor DNA (ctDNA) to see if we can improve our ability to detect the spread of invasive lobular cancer.
